The overall goal of the proposed research is to investigate the roles of cellular homologs of retroviral transforming genes in non-virus induced neoplasms. Transforming genes detected by transfection of tumor DNAs will be compared with retroviral transforming genes by nucleic acid hybridization. Since the transforming genes of human bladder and lung carcinomas are cellular homologs of the ras genes of Harvey and Kirsten sarcoma viruses, we will investigate the range of carcinomas in which activated ras genes can be detected. Molecular clones of ras genes activated in neoplams will be compared with molecular clones of normal cell ras genes to determine the alterations responsible for activation of transforming potential during carcinogenesis. Expression of these genes in carcinomas and normal cells will be studied to investigate the correlation between gene expression and activation of transforming activity during neoplasia.